Intermittent pacing therapy favorably modulates infarct remodeling

André Uitterdijk, Tirza Springeling, Kevin C.M. Hermans, Daphne Merkus, Vincent J. de Beer, Charlotte Gorsse-Bakker, Eric Mokelke, Evangelos P. Daskalopoulos, Piotr A. Wielopolski, Jack P.M. Cleutjens, W. Matthijs Blankesteijn, Frits W. Prinzen, Willem J. van der Giessen, Robert Jan M. van Geuns, Dirk J. Duncker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content.

Original languageEnglish
Article number28
JournalBasic Research in Cardiology
Volume112
Issue number3
DOIs
Publication statusPublished - 6 Apr 2017

Bibliographical note

Funding Information:
This study was financially supported by Boston Scientific/Guidant. Eric Mokelke is a former Boston Scientific Employee.

Publisher Copyright:
© 2017, The Author(s).

Research programs

  • EMC NIHES-03-30-02

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